The hypothesis that N-nitroso compounds are carcinogenic because they are converted to direct alkylating agents by only target tissues is attractive, but most studies designed to test the hypothesis have investigated formation of alkylated bases only after a single administration of a near lethal dose of carcinogen which may be pharmacokinetically unrelated to environmental exposures. Proposed studies will continue examining quantitatively the chemical nature and extent of alkylation of DNA in liver, kidney, lung, pancreas, and colon by five carcinogens which are converted to alkylating agents at widely different rates by these tissues. Sensitivities of these tissues to carcinogenic activities of 1,2-dimethylhydrazine, diethylnitrosamine, N-nitrosopyrrolidine, N-nitrosomorpholine, and methylnitrosourea are established and are being used as comparators with site of alkylation. Adult rats and hamsters will be given single doses of diethylnitrosamine ranging from 1/16 to 1 LD50 and ethylation of DNA will be quantitated over the following 216 hr. A similar study will be done with methylnitrosourea in guinea pigs. Also, ethylation of DNA during chronic administration of low levels of diethylnitrosamine to rats will be measured in target and non-target tissue. Isolation, silylation, and gas chromatography - mass spectrometry analysis of newly detected DNA adducts in N-nitrosopyrrolidine- and N-nitrosomorpholine-treated rats will be pursued.